Toward optimization of target planning for magnetic resonance image-targeted, 3D transrectal ultrasound-guided fusion prostate biopsy

The current clinical standard for diagnosis of prostate cancer (PCa) is 2D transrectal ultrasound (TRUS)-guided biopsy. However, this procedure has a false negative rate of 21-47% and therefore many patients return for repeat biopsies. A potential solution for improving upon this problem is “fusion” biopsy, where magnetic resonance imaging (MRI) is used for PCa detection and localization prior to biopsy. In this procedure, tumours are delineated on pre-procedural MRI and registered to the 3D TRUS needle guidance modality. However, fusion biopsy continues to yield false negative results and there remains a gap in knowledge regarding biopsy needle target selection. Within-tumour needle targets are currently chosen ad hoc by the operating clinician without accounting for guidance system and registration errors. The objective of this thesis was to investigate how the choice of target selection strategy and number of biopsy attempts made per lesion may affect PCa diagnosis in the presence of needle delivery error. A fusion prostate biopsy simulation software platform was developed, which allowed for the investigation of how needle delivery error affects PCa diagnosis and cancer burden estimation. Initial work was conducted using 3D lesions contoured on MRI by collaborating radiologists. The results indicated that more than one core must be taken from the majority of lesions to achieve a sampling probability 95% for a biopsy system with needle delivery error ≥ 3.5 mm. Furthermore, it was observed that the optimal targeting scheme depends on the relative levels of systematic and random needle delivery errors inherent to the specific fusion biopsy system. Lastly, PCa tumours contoured on digital histology images by genitourinary pathologists were used to conduct biopsy simulations. The results demonstrated that needle delivery error has a substantial impact on the biopsy core involvement observed, and that targeting of high-grade lesions may result in higher core involvement variability compared with lesions of all grades. This work represents a first step toward improving the manner in which lesions are targeted using fusion biopsy. Successful integration of these findings into current fusion biopsy system operation could lead to earlier PCa diagnosis with the need for fewer repeat biopsy procedures

Flow simulation of a natural polymer in a syringe-needle delivery device

Neurodegenerative diseases, such as Parkinson's disease, affect a large num- ber of the erderly population and still remain untreated. In recent years, cell therapy has emerged as a promising therapeutic strategy. To increase cell viability, biomaterials are of- ten used as scaffolds and facilitate cell deposition, through injection, to the site of interest. However, fluid forces acting on the cells during injection may lead to their disruption or death. This study aims to develop a novel device for the delivery of a cell-embedded, in situ forming, collagen hydrogel. A preliminary simulation study on constricted channels rep- resenting the syringe was performed to gain insight into the effect of needle diameter and syringe geometry. Straight needles emanating co-axially from syringes of various geome- tries were computationally modelled in the two-dimensional space, using OpenFOAMⓇ. The natural collagen solution was modelled as a continuum medium, without cells, and the flow was assumed incompressible, with non-Newtonian fluid constitutive behaviour. The effects of needle diameter and syringe geometry on velocity and shear stresses were examined. The results highlight the importance of geometric characteristics on the design of new cell delivery devices. If cells pass from the syringe barrel to the needle, the pressure drop and the increased velocity could damage them. This is more likely to occur using higher Gauge needles. Further analysis is required including simulations of cells during injection and analysis of their deformation

Ultra-High Field Strength MR Image-Guided Robotic Needle Delivery Device for In-Bore Small Animal Interventions

Current methods of accurate soft tissue injections in small animals are prone to many sources of error. Although efforts have been made to improve the accuracy of needle deliveries, none of the efforts have provided accurate soft tissue references. An MR image-guided robot was designed to function inside the bore of a 9.4T MR scanner to accurately deliver needles to locations within the mouse brain. The robot was designed to have no noticeable negative effects on the image quality and was localized in the MR images through the use of an MR image visible fiducial. The robot was mechanically calibrated and subsequently validated in an image-guided phantom experiment, where the mean needle targeting accuracy and needle trajectory accuracy were calculated to be 178 ± 54µm and 0.27 ± 0.65º, respectively. Finally, the device successfully demonstrated an image-guided needle targeting procedure in situ

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Safety, feasibility, and outcomes of transcaval access for the delivery of Impella microaxial-flow pump 5.0 in patients with acute heart failure

Background: Transcaval access (TCA) may enable fully percutaneous mechanical circulatory support (MCS) without the hazards of vascular complication in patients with heart failure that require left ventricular unloading. Purpose: To review the safety, feasibility, and outcomes of using TCA to deliver Impella 5.0 MCS in patients with ischemic and non-ischemic systolic acute heart failure. Methods: This single center retrospective study included all patients that underwent TCA placement of a 5.0 Impella from June 2015 to January 2021. Demographic, clinical and procedural variables, and in-hospital outcomes were collected. The procedure was performed by electrifying a caval guidewire and advancing it into a pre-positioned aortic snare. After exchanging for a rigid guidewire, a 22 or 24Fr sheath was delivered into the aorta and then the Impella 5.0 was placed in the left ventricle through TCA sheaths. Results: A total of 43 patients were included in the analysis. The average age was 56.9 years (interquartile range [IQR], 52-65.5), of which, 70%(n=30) were males. Fifteen patients had non-ischemic cardiomyopathy and 28 had ischemic cardiomyopathy. Baseline average left ventricular ejection fraction prior to implantation was 23.6% (IQR, 13.75-29.75). 86% of the patients were in category C-D of the SCAI classification schema for cardiogenic shock (CS), 39.5% required inotropes and 48.8% required pressors prior to the procedure; 54% had a prior MCS in place. Only 18.6% of the cases had prior CT imaging reviewed for planning. TCA was successful in all attempted patients and the MCS delivery was achieved in 100% of the cohort. The available hemodynamic parameters prior and after Impella 5.0 implantation via Table 1 TCA are summarized in table 1. From the total cohort, only 29 patients survived to explant device and TCA sheath. The explant was successful in all patients using nitinol occluders; two patients required a covered stent at the arteriotomy site due to right sided heart failure from residual fistula; no surgical repair was necessary. All residual fistulous tracks were graded as1 from Impella insertion/removal site was observed in 9.3%,which didn\u27t require further intervention. No vascular complication of the access site was observed with TCA. During hospitalization, 20.9% had VT/VF and 4.7% a PEA after implantation (all CS patients). 13.9% of the patients had AKI requiring hemodialysis and no stroke was observed in the entire group. The average length of stay for entire cohort was 16.3 days (IQR, 3.25-18.75). Conclusions: Transcaval access of 5.0 Impella is safe and feasible under expert hands for patients where more conventional MCS devices do not provide enough support or have inadequate peripheral arterial access

Interventional multispectral photoacoustic imaging with a clinical ultrasound probe for discriminating nerves and tendons: an ex vivo pilot study

Abstract. Accurate and efficient identification of nerves is an essential component of peripheral nerve blocks. While ultrasound (US) imaging is increasingly used as a guidance modality, it often provides insufficient contrast for identifying nerves from surrounding tissues such as tendons. Electrical nerve stimulators can be used in conjunction with US imaging for discriminating nerves from surrounding tissues, but they are insufficient to reliably prevent neural punctures, so that alternative methods are highly desirable. In this study, an interventional multispectral photoacoustic (PA) imaging system was used to directly compare the signal amplitudes and spectra acquired from nerves and tendons ex vivo, for the first time. The results indicate that the system can provide significantly higher image contrast for discriminating nerves and tendons than that provided by US imaging. As such, photoacoustic imaging could be valuable as an adjunct to US for guiding peripheral nerve blocks

Developing a blockchain-based supply chain system for advanced therapies: study protocol

Advanced therapies, including cell and gene therapies, have shown therapeutic promise in curing life-threatening diseases such as leukaemia and lymphoma. However, they can be complicated and expensive to deliver due to their sensitivity to environment, troublesome tissue, cell, or genetic material sourcing and complicated regulatory requirements

New Technology and Techniques for Needle-Based Magnetic Resonance Image-Guided Prostate Focal Therapy

The most common diagnosis of prostate cancer is that of localized disease, and unfortunately the optimal type of treatment for these men is not yet certain. Magnetic resonance image (MRI)-guided focal laser ablation (FLA) therapy is a promising potential treatment option for select men with localized prostate cancer, and may result in fewer side effects than whole-gland therapies, while still achieving oncologic control. The objective of this thesis was to develop methods of accurately guiding needles to the prostate within the bore of a clinical MRI scanner for MRI-guided FLA therapy. To achieve this goal, a mechatronic needle guidance system was developed. The system enables precise targeting of prostate tumours through angulated trajectories and insertion of needles with the patient in the bore of a clinical MRI scanner. After confirming sufficient accuracy in phantoms, and good MRI-compatibility, the system was used to guide needles for MRI-guided FLA therapy in eight patients. Results from this case series demonstrated an improvement in needle guidance time and ease of needle delivery compared to conventional approaches. Methods of more reliable treatment planning were sought, leading to the development of a systematic treatment planning method, and Monte Carlo simulations of needle placement uncertainty. The result was an estimate of the maximum size of focal target that can be confidently ablated using the mechatronic needle guidance system, leading to better guidelines for patient eligibility. These results also quantified the benefit that could be gained with improved techniques for needle guidance

False positives in PIRADS (V2) 3, 4, and 5 lesions:relationship with reader experience and zonal location

PURPOSE: To investigate the effect of reader experience and zonal location on the occurrence of false positives (FPs) in PIRADS (V2) 3, 4, and 5 lesions on multiparametric (MP)-MRI of the prostate. MATERIALS AND METHODS: This retrospective study included 139 patients who had consecutively undergone an MP-MRI of the prostate in combination with a transrectal ultrasound MRI fusion-guided biopsy between 2014 and 2017. MRI exams were prospectively read by a group of inexperienced radiologists (cohort 1; 54 patients) and an experienced radiologist (cohort 2; 85 patients). Multivariable logistic regression analysis was performed to determine the association of experience of the radiologist and zonal location with a FP reading. FP rates were compared between readings by inexperienced and experienced radiologists according to zonal location, using Chi-square (χ2) tests. RESULTS: A total of 168 lesions in 139 patients were detected. Median patient age was 68 years (Interquartile range (IQR) 62.5-73), and median PSA was 10.9 ng/mL (IQR 7.6-15.9) for the entire patient cohort. According to multivariable logistic regression, inexperience of the radiologist was significantly (P = 0.044, odds ratio 1.927, 95% confidence interval [CI] 1.017-3.651) and independently associated with a FP reading, while zonal location was not (P = 0.202, odds ratio 1.444, 95% CI 0.820-2.539). In the transition zone (TZ), the FP rate of the inexperienced radiologists 59% (17/29) was significantly higher (χ2P = 0.033) than that of the experienced radiologist 33% (13/40). CONCLUSION: Inexperience of the radiologist is significantly and independently associated with a FP reading, while zonal location is not. Inexperienced radiologists have a significantly higher FP rate in the TZ

DNA Immunization for HIV Vaccine Development

DNA vaccination has been studied in the last 20 years for HIV vaccine research. Significant experience has been accumulated in vector design, antigen optimization, delivery approaches and the use of DNA immunization as part of a prime-boost HIV vaccination strategy. Key historical data and future outlook are presented. With better understanding on the potential of DNA immunization and recent progress in HIV vaccine research, it is anticipated that DNA immunization will play a more significant role in the future of HIV vaccine development